CN1652806A - Preparation for treating male and female sexual impotence - Google Patents

Abstract

The present invention discloses a pharmaceutical composition comprising extracts of Tribulus terrestris, turnera diffusa and Cinnamomum cassia in a weight ratio of 1.5-3.5: 1-2: 0.1-0.4, respectively; ginkgo biloba extract and optionally arginine or a physiologically equivalent ester, salt or precursor thereof. The compositions of the invention are useful for the treatment of male and female sexual dysfunction.

Description

Preparations useful in the treatment of male and female impotence

Description of the invention

The present invention relates to formulations useful in the treatment of male and female sexual dysfunction.

Sexual dysfunction is of considerable importance and forms the subject of a wide range of biomedical research efforts. According to recent statistics, various forms of impotence (lack of libido and erectile dysfunction) affect approximately 70% of the population aged approximately 50 years and over. The various forms of impotence vary markedly in severity, especially in the elderly, where impotence is often physiologically related to other conditions such as heart or kidney disease.

Drugs currently available for the treatment of such dysfunction, especially erectile dysfunction, include hormones such as testosterone, VIP, prostaglandin derivatives ( _PGEs ), and cardiovascular drugs such as papaverine, phenoxybenzamine, and phentolamine.

However, none of these drugs offers a satisfactory, permanent solution to this problem due to the side effects they cause and the need for, for example, papaverine and PGEs, intracavitary or intraurethral injections.

More recently, cGMP phosphodiesterase inhibitors have been developed, which are especially useful in the treatment of impotence and are active via the oral route. One of these drugs, the so-called sildenafil (WO 94/28902) is on the market.

Also, side effects are still not negligible, so safer and more effective treatments are still urgently needed.

A large number of products of natural origin (mainly based on plants but also animals) are now being studied with the aid of modern pharmacology based on the indications of traditional medicine in order to assess the possible scientific basis for their empirical use.

Biochemical studies have demonstrated that extremely complex mechanisms are involved in the physiological processes involved in sexual activity such as penile and clitoral erection, vaginal lubrication, ejaculation and orgasm.

Mediators such as nitric oxide (NO), enzyme factors involved in the metabolism of cAMP and cGMP messengers, adrenergic receptors of smooth muscle cell membranes, dopaminergic neurotransmitters and receptors for _PGEs or other hormones are impotence and other sexual dysfunctions possible targets for pharmacological treatment.

Clearly, it is difficult to provide a satisfactory solution to this particular problem, in part because, in addition to purely biochemical and physiological factors, there are environmental and psychological factors.

It has now been found that certain dosage ratios of combinations of medicinal plant extracts having specific properties lead to particularly satisfactory therapeutic results in the treatment of male and female sexual dysfunction.

The present discovery relates in particular to pharmaceutical compositions comprising:

Extracts of Tribulus terrestris, Turnera diffusa and Cinnamon cassia in a weight ratio of 1.5-3.5:1-2:0.1-0.4;

Ginkgo biloba extract, and possibly

- Mixtures of arginine or its physiologically equivalent esters, salts or precursors with suitable carriers or excipients.

Extracts of Tribulus terrestris, Turnergrass and cinnamon are known and used in some types of traditional medicines for similar purposes, but their combination is unknown, let alone in the specific dosage ratios mentioned above.

In particular, Tribulus terrestris extract is known to induce the synthesis of testosterone, a hormone that stimulates libido in both men and women; Tribulus terrestris extract is rich in essential oil, which has a vasodilation effect regulated by NO release, so the extract has a positive effect on arterial and arterioles exert vasodynamic activity; cinnamon extract indirectly stimulates libido by acting on dopaminergic receptors associated with pleasure.

Finally, the dimeric flavonoids extracted from Ginkgo biloba have strong anti-phosphodiesterase activity, which contributes to the dilation of blood vessels in the corpus cavernosum, thereby enhancing the vascular effect of Tenewort.

However, the therapeutic results obtainable with the composition of the invention cannot be explained based on the activity of each extract alone. In fact, it has surprisingly been found that when the individual extracts are combined in ratios different from those described above, they are inactive and may even aggravate the disorder. Therefore, a real improvement in sexual activity can only be obtained when extracts of various plants are used in precise proportions to increase libido and blood supply to the sex organs.

The weight ratio of the extracts of Tribulus terrestris, Herba terrestris and cinnamon is preferably 2.5:1.5:0.2.

When arginine, its salt, ester or precursor is used, the ratio of its usage to the plant extract is 0.5 to 1.5, preferably 1.

Ginkgo biloba extract preferably consists of the apigenin dimeric flavonoid fraction, preferably added to the composition of the invention in a dose ensuring a daily intake of said fraction of 50 mg.

The medicinal plant extracts indicated above, obtained by conventional techniques such as extraction with solvents or supercritical fluids, can be used for the purpose of the present invention.

However, it is preferred to use standardized extracts having predetermined amounts of certain characteristic extract components.

For example, an extract of Tribulus terrestris may contain about 40% saponins expressed as diosgenin; an extract of turnerwort is preferably a lipophilic extract; an extract of ginkgo biloba preferably has a dimeric flavonoid content of about 60%; and an extract of cinnamon preferably has About 70% cinnamaldehyde content.

In preparing the extract, various parts of the plant can be used as they contain different concentrations of the active ingredient. In particular, the whole plant is used in the preparation of the tuna extract, preferably with carbon dioxide under supercritical conditions, at a pressure of 230 to 250 bar, preferably 240 bar, at a temperature of 35 to 55°C, preferably 40°C Extraction; Tribulus extract is preferably obtained from the aerial parts and seeds of the plant by extraction with a 40% ethanol/water mixture, while cinnamon extract is preferably obtained by using Carbon dioxide, prepared by extracting from the bark of the trunk at a temperature of 35°C. Ginkgo biloba extract is preferably prepared from a fraction composed of dimeric flavonoids derived from apigenin, eg prepared according to EP360556.

The present invention also relates to extracts of Tribulus terrestris, turner grass and cinnamon and ginkgo biloba and optionally arginine or its physiologically equivalent esters, salts or Use of the precursors for the manufacture of a medicament for the treatment of male and female sexual dysfunction, in particular for the treatment of impotence, libido disorders, frigidity and ansexuality.

The mixture of extracts involved in the present invention must be taken chronically, not just immediately before intercourse, although in some individuals, the first treatment responds within 30 minutes of taking the dose.

As an alternative to plant extracts, it is possible to use the corresponding isolated active ingredients, in particular dioscin, ginkgo biloba flavonoids and cinnamaldehyde in combination with the lipophilic tumegrain extract. The use of said combination for the preparation of a medicament for the treatment of impotence, erectile dysfunction, libido disorder, frigidity and anerogeny and a medicament comprising said combination is another object of the present invention.

Long-term administration of the composition of the invention does not cause any significant side effects, is well tolerated, and does not alter the delicate hormonal balance, in particular the androgen/estrogen balance, which controls major physiological events in men and women such as Andropause and menopause.

Examples of suitable administration forms of the composition of the present invention include tablets, soft and hard gelatin capsules, suppositories and drinks containing a unit dose of 100 mg to 300 mg of Tribulus terrestris extract and other components in the above weight ratios of the unit dose. Particular preference is given to solid formulations such as unmodified release or gastric resistant tablets or drinkable liquid forms.

The following examples are given to illustrate the invention without limiting its scope.

Example 1 - Preparation of Coated Tablets

Each 700mg coated tablet contains:

Tribulus Terrestris 250.00mg

Turner Grass 150.00mg

Cinnamon 20.00mg

Ginkgo Biloba 50.00mg

L-Arginine 100.00mg

Soybean Polysaccharide 55.00mg

Silica 14.00mg

Silicified Microcrystalline Cellulose 42.00mg

Magnesium stearate 4.00mg

Hydroxypropyl Methyl Cellulose 6.40mg

Talc 5.20mg

Titanium Dioxide 2.00mg

Glycerin 0.12mg

Polysorbate 80 0.80mg

Quinoline 0.43mg

Indigo 0.05mg

Example 2 - Preparation of Hard Gelatin Capsules

Each 340mg capsule contains:

Tribulus Terrestris 125.00mg

Turner Grass 75.00mg

Cinnamon 10.00mg

Ginkgo Biloba 25.00mg

L-Arginine 50.00mg

Soybean Polysaccharide 25.00mg

Silica 7.00mg

Silicified microcrystalline cellulose 20.00mg

Magnesium stearate 1.50mg

Talc 1.50mg

The preparation of embodiment 3-soft gelatin capsules

Each 700mg soft gelatin capsule contains:

Tribulus Terrestris 125.00mg

Turner Grass 75.00mg

Cinnamon 10.00mg

Ginkgo Biloba 25.00mg

L-Arginine 50.00mg

Soy Lecithin 20.00mg

Medium Chain Triglycerides 100.00mg

Polysorbate 80 10.00mg

Soybean Oil 275.00mg

Colloidal silicon dioxide 10.00mg

Example 4 - Preparation of Potable Solution

Each 10ml vial contains:

Tribulus Terrestris 250.00mg

Turner Grass 150.00mg

Cinnamon 20.00mg

Ginkgo Biloba 50.00mg

L-arginine hydrochloride 100.00mg

Glycerin 3000.00mg

Polysorbate 20 800.00mg

Propylene glycol 1000.00mg

Acesulfame K 175.00mg

Sodium Saccharin 40.00mg

Neohesperidin DC 2.50mg

Flavoring agent 300.00mg

Potassium sorbate 11.70mg

Methylparaben 8.30mg

Purified water Appropriate amount to 10.00ml

Preparation of embodiment 5-soluble granules

Each 5000mg capsule contains:

Tribulus Terrestris 250.00mg

Turner Grass 150.00mg

Cinnamon 20.00mg

Ginkgo Biloba 50.00mg

L-arginine hydrochloride 100.00mg

Polysorbate 20 500.00mg

Acesulfame K 175.00mg

Sodium Saccharin 40.00mg

Neohesperidin DC 2.50mg

Flavoring agent 300.00mg

Inulin 1000.00mg

Mannitol 2412.50mg

Claims (10)

1. pharmaceutical composition, contain:

● weight ratio is respectively 1.5-3.5: 1-2: the Fructus Tribuli of 0.1-0.4, Turnera diffusa and Cortex Cinnamomi extract,

● Semen Ginkgo extrac and randomly

● arginine or its physiology go up suitable ester, salt or precursor and the carrier that suits or the mixture of excipient.

2. the described compositions of claim 1, wherein the weight ratio of Fructus Tribuli, Turnera diffusa and Cortex Cinnamomi extract is 2.5: 1.5: 0.2.

3. claim 1 or 2 described compositionss, wherein Semen Ginkgo extrac is grouped into by apigenin dimeric flavonoids level.

4. the described compositions of claim 3 contains 50mg apigenin dimeric flavonoids fraction.

5. each described compositions in the claim 1 to 4 contains weight ratio and is respectively 1.5-3.5: 1-2: 0.1-0.4: the Fructus Tribuli of 0.5-1.5, Turnera diffusa and Cortex Cinnamomi extract and L-arginine or L-arginine monohydrochloride.

6. the described compositions of claim 5, wherein the weight ratio of Fructus Tribuli, Turnera diffusa and Cortex Cinnamomi extract and L-arginine or L-arginine monohydrochloride is 2.5: 1.5: 0.2: 1.

7. weight ratio is respectively 1.5-3.5: 1-2: the combination of the Fructus Tribuli of 0.1-0.4, Turnera diffusa and Cortex Cinnamomi extract and Semen Ginkgo extrac and randomly arginine or its physiology go up suitable ester, salt or precursor and be used for the treatment of purposes in the medicine of male and female sexual dysfunction in preparation.

8. the described purposes of claim 7 is used for the treatment of sexual dysfunction, erection disturbance, dysaphrodisia, hyposexuality and frigidity.

9. pharmaceutical composition comprises lipophilic extract, Ginkgo dimerization flavone and the cinnamic aldehyde of dioscin, Turnera diffusa.

10. the lipophilic extract of dioscin, Turnera diffusa, Ginkgo dimerization flavone and cinnamic aldehyde are used for the treatment of purposes in the medicine of male and female sexual dysfunction in preparation.